Effect of transmitted drug resistance on virological and immunological response to initial combination antiretroviral therapy for HIV (EuroCoord-CHAIN joint project): a European multicohort study
Effect of transmitted drug resistance on virological and immunological response to initial combination antiretroviral therapy for HIV (EuroCoord-CHAIN joint project): a European multicohort study
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DOI：
10.1016/s1473-3099(11)70032-9
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发表时间：
2011-05-01
影响因子：
56.3
通讯作者：
Chene, Genevieve
中科院分区：
文献类型：
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作者：
Wittkop, Linda;Guenthard, Huldrych F.;Chene, Genevieve
背景传播性耐药（TDR）对HIV-1一线联合抗逆转录病毒治疗（cART）的影响需要进一步研究，以指导最佳药物方案的选择。我们在一个大型欧洲合作项目中调查了TDR对cART第一年结果的影响。方法纳入1998年1月1日以后首次开始抗逆转录病毒治疗（至少三种抗逆转录病毒药物）的任何年龄的艾滋病毒感染者，并且在开始抗逆转录病毒治疗之前至少进行了一次基因型检测。我们使用世卫组织耐药清单和斯坦福算法将患者分为三种耐药类别：没有TDR，至少有一种突变和完全活跃的cART，或至少有一种突变和对至少一种处方药耐药。病毒学失败定义为治疗6个月后，两次连续病毒载量测量超过500拷贝/ mL的时间。来自25个队列的10056例患者中，9102例（90.5%）患有无TDR的HIV， 475例（4.7%）至少有一种突变但接受了完全有效的CART治疗，479例（4.8%）至少有一种突变并对至少一种药物耐药。无TDR组患者12个月病毒学失败的累积Kaplan-Meier估计为4.2% (95% CI 3.8-4.7)， TDR和完全活性CART组患者为4.7% (2.9-7.5)，TDR和耐药组患者为15.1% （11.9-19.0）
Background The effect of transmitted drug resistance (TDR) on first-line combination antiretroviral therapy (cART) for HIV-1 needs further study to inform choice of optimum drug regimens. We investigated the effect of TDR on outcome in the first year of cART within a large European collaboration.Methods HIV-infected patients of any age were included if they started cART (at least three antiretroviral drugs) for the first time after Jan 1,1998, and were antiretroviral naive and had at least one sample for a genotypic test taken before the start of cART. We used the WHO drug resistance list and the Stanford algorithm to classify patients into three resistance categories: no TDR, at least one mutation and fully-active cART, or at least one mutation and resistant to at least one prescribed drug. Virological failure was defined as time to the first of two consecutive viral load measurements over 500 copies per mL after 6 months of therapy.Findings Of 10 056 patients from 25 cohorts, 9102 (90.5%) had HIV without TDR, 475 (4.7%) had at least one mutation but received fully-active CART, and 479 (4.8%) had at least one mutation and resistance to at least one drug. Cumulative Kaplan-Meier estimates for virological failure at 12 months were 4.2% (95% CI 3.8-4.7) for patients in the no TDR group, 4.7% (2.9-7.5) for those in the TDR and fully-active CART group, and 15.1% (11.9-19.0) for those in the TDR and resistant group (log-rank p